Proteasome-mediated mineralocorticoid receptor degradation attenuates transcriptional response to aldosterone.

Abstract:

:The ubiquitin-proteasome pathway regulates the turnover of many nuclear hormone receptors, such as the estrogen receptor. For estrogen receptor, proteasome inhibition decreases ligand-mediated transcription. We provide evidence that the mineralocorticoid receptor (MR) is degraded by the ubiquitin-proteasome pathway in a ligand-dependent manner and that proteasomal inhibition results in increased accumulation of the MR with enhancement of transcriptional response to aldosterone. Examination of the primary sequence of human and rat MR has identified two candidate PEST degradation motifs. Mutation of lysine 715 and/or 367 within this PEST element failed to prevent degradation of MR protein or transcriptional activity mediated by aldosterone, indicating that other lysine residues are targeted by proteasomal degradation of MR. These findings demonstrate a coupling between MR up-regulation and transcriptional hyperactivity.

journal_name

Endocr Res

journal_title

Endocrine research

authors

Yokota K,Shibata H,Kobayashi S,Suda N,Murai A,Kurihara I,Saito I,Saruta T

doi

10.1081/erc-200043783

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

611-6

issue

4

eissn

0743-5800

issn

1532-4206

journal_volume

30

pub_type

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